Recent progress in the search for synthetic active pharmaceutical substances having similar or superior antithrombotic properties when compared to heparin, has resulted in the design of new dual inhibitors e.g. as described in WO 99/65934 and WO 01/42262. Those compounds are typically conjugates of an oligosaccharide residue connected to a direct thrombin inhibitor by an essentially pharmacologically inactive spacer. The oligosaccharide residue in the molecule displays anti-thrombin III (AT-III) mediated anti-Xa activity. Thus, the new conjugates have dual, antithrombotic and anticoagulant, activity.
An excellent example of the new class of dual inhibitors is the compound indicated with the code name Org 42675, in which a pentasaccharide is linked to a direct inhibitor of thrombin, having the following structure:

Studies in experimental thrombosis have demonstrated that this compound, in addition to potent anticoagulant and antithrombotic properties, also inhibits the activity of clot-bound thrombin. Further, Org 42675 appeared to be highly efficacious in the prevention of thrombotic reocclusion following thrombolysis of occlusive arterial thrombi. The compound displays a 10-fold prolonged half-life in comparison to the corresponding non-conjugated direct thrombin inhibitor derived from NAPAP. In comparison with argatroban, heparin and fondaparinux, Org 42675 showed improved efficacy. (Journal of Thrombosis and Haemostasis, Volume 1, Issue 9, Page 1945, 2003).
The clinical potential of the new dual inhibitors is considered to be significant and therefore clinical testing has already been initiated.